RAD52

1H2I, 1KN0589319365ENSG00000002016ENSMUSG00000030166P43351P43352NM_134423NM_134424NM_001166381NM_001166382NM_001166383NM_011236NP_001284348NP_001284349NP_001284350NP_001284351NP_602296NP_001159853NP_001159854NP_001159855NP_035366RAD52 homolog (S. cerevisiae), also known as RAD52, is a protein which in humans is encoded by the RAD52 gene.1h2i: HUMAN RAD52 PROTEIN, N-TERMINAL DOMAIN1kn0: Crystal Structure of the human Rad52 protein RAD52 homolog (S. cerevisiae), also known as RAD52, is a protein which in humans is encoded by the RAD52 gene. The protein encoded by this gene shares similarity with Saccharomyces cerevisiae Rad52, a protein important for DNA double-strand break repair and homologous recombination. This gene product was shown to bind single-stranded DNA ends, and mediate the DNA-DNA interaction necessary for the annealing of complementary DNA strands. It was also found to interact with DNA recombination protein RAD51, which suggested its role in RAD51-related DNA recombination and repair. RAD52 mediates RAD51 function in homologous recombinational repair (HRR) in both yeast Saccharomyces cerevisiae and in mammalian cells of mice and humans. However, the RAD52 protein has distinctly different functions in HRR of yeast and humans. In S. cerevisae, Rad52 protein, acting alone, facilitates the loading of Rad51 protein onto single-stranded DNA pre-coated with replication protein A in the presynaptic phase of recombination. In mice and humans, however, BRCA2 primarily mediates orderly assembly of RAD51 on ssDNA, the form that is active for homologous pairing and strand invasion. BRCA2 also redirects RAD51 from dsDNA and prevents dissociation from ssDNA. In addition, the four paralogs of RAD51, consisting of RAD51B (RAD51L1), RAD51C (RAD51L2), RAD51D (RAD51L3), XRCC2 form a complex called the BCDX2 complex. This complex participates in RAD51 recruitment or stabilization at damage sites. The BCDX2 complex appears to act by facilitating the assembly or stability of the RAD51 nucleoprotein filament. However, in the presence of a BRCA2 mutation, human RAD52 can mediate RAD51 assembly on ssDNA and substitute for BRCA2 in homologous recombinational DNA repair, though with lower efficiency than BRCA2. In addition, human RAD52, in combination with ERCC1, promotes the error-prone homologous DNA repair pathway of single-strand annealing. Though error prone, this repair pathway may be needed for survival of cells with DNA damage that is not otherwise repairable. Human RAD52 also has an important role in repair of DNA double-strand breaks at active transcription sites during the G0/G1 phase of the cell cycle. Repair of these double-strand breaks appears to use an RNA template-based recombination mechanism dependent on RAD52. The Cockayne Syndrome B protein (CSB) (coded for by ERCC6) localizes at double-strand breaks at sites of active transcription, followed by RAD51, RAD51C and RAD52 to carry out homologous recombinational repair using the newly synthesized RNA as a template. Three prime untranslated regions (3'UTRs) of messenger RNAs (mRNAs) often contain regulatory sequences that can cause post-transcriptional RNA silencing. Such 3'-UTRs often contain binding sites for microRNAs (miRNAs). By binding to specific sites within the 3'-UTR, miRNAs can decrease gene expression of various mRNAs by either inhibiting translation or directly causing degradation of the transcript. MicroRNAs (miRNAs) appear to regulate the expression of more than 60% of protein coding genes of the human genome. One microRNA, miR-210, represses RAD52. As noted by Devlin et al., miR-210 is up-regulated in most solid tumors and negatively affects the clinical outcome. The 3'-UTR of RAD52 also has a binding site for the microRNA let-7. Women with a single-nucleotide polymorphism (SNP) in the binding site for let-7 (rs7963551), that causes reduced binding of let-7, likely have increased expression of RAD52 (as was shown for this SNP in liver). Women with this SNP in the 3'UTR of RAD52 showed a reduced breast cancer risk with an odds ratio of 0.84, 95% confidence interval of 0.75-0.95.